Mesalamine Rectal

Description

Mesalamine Rectal Suppository contains 1000 mg of mesalamine, also known as mesalazine or 5-aminosalicylic acid (5-ASA), as the active ingredient for rectal use. Mesalamine is chemically defined as 5-amino-2-hydroxybenzoic acid and is classified as an aminosalicylate. Each suppository is formulated with mesalamine (USP) in a base of Hard Fat, NF. The empirical formula of mesalamine is C₇H₇NO₃, which corresponds to a molecular weight of 153.14.

Uses and Indications

Mesalamine Rectal Suppositories are indicated in adults for the treatment of mildly to moderately active ulcerative proctitis.

There are no teratogenic or nonteratogenic effects associated with the use of this medication.

Dosage and Administration

The recommended adult dosage of Mesalamine Rectal Suppositories is 1000 mg, administered rectally once daily at bedtime for a duration of 3 to 6 weeks. The safety and effectiveness of this treatment beyond 6 weeks have not been established.

Prior to initiating therapy with Mesalamine Rectal Suppositories, healthcare professionals should evaluate the patient's renal function and continue to monitor it periodically throughout the treatment course.

It is important to instruct patients not to cut or break the suppository prior to administration. Patients should also be advised to maintain adequate hydration by drinking an appropriate amount of fluids. After insertion, the suppository should be retained for a minimum of one to three hours, or longer if possible, to maximize therapeutic effect.

Contraindications

Use is contraindicated in patients with known or suspected hypersensitivity to salicylates or aminosalicylates, or to any components of the formulation. This contraindication is based on the potential for severe allergic reactions in susceptible individuals.

Warnings and Precautions

Patients with renal impairment require careful evaluation of the risks and benefits associated with the use of Mesalamine Rectal Suppositories. It is essential to monitor renal function closely, and treatment should be discontinued if there is any deterioration in renal status.

Mesalamine may induce an acute intolerance syndrome, which can present symptoms that are challenging to differentiate from an exacerbation of ulcerative colitis. Healthcare professionals should monitor patients for any worsening of symptoms and discontinue treatment if acute intolerance syndrome is suspected.

Hypersensitivity reactions, including myocarditis and pericarditis, necessitate immediate evaluation. If a hypersensitivity reaction is suspected, Mesalamine treatment should be discontinued promptly.

In patients with known liver impairment, a thorough assessment of the risks and benefits is warranted prior to initiating therapy.

Severe cutaneous adverse reactions may occur; therefore, it is critical to discontinue Mesalamine at the first signs or symptoms of such reactions or any other indications of hypersensitivity. Further evaluation should be considered in these cases.

Patients should be advised about the risk of photosensitivity. Those with pre-existing skin conditions should take precautions to avoid sun exposure, including wearing protective clothing and applying a broad-spectrum sunscreen when outdoors.

The potential for nephrolithiasis should be communicated to patients, as Mesalamine-containing stones are not detectable by standard radiography or computed tomography (CT). Adequate hydration during treatment is essential to mitigate this risk.

It is important to note that Mesalamine can interfere with laboratory tests for urinary normetanephrine. Specifically, spuriously elevated results may occur with liquid chromatography using electrochemical detection. Therefore, alternative selective assays for normetanephrine should be utilized in patients receiving Mesalamine Rectal Suppositories.

Side Effects

Patients receiving Mesalamine Rectal Suppositories may experience a range of adverse reactions. Common adverse reactions, occurring in 1% or more of patients, include dizziness, rectal pain, fever, rash, acne, and colitis.

Serious adverse reactions have been reported and require careful monitoring. Renal impairment is a significant concern; patients with known renal impairment or those taking nephrotoxic drugs should have their renal function evaluated regularly. Mesalamine Rectal Suppositories should be discontinued if renal function deteriorates. Additionally, Mesalamine-Induced Acute Intolerance Syndrome may present symptoms that are difficult to distinguish from an exacerbation of ulcerative colitis. Monitoring for worsening symptoms is essential, and treatment should be discontinued if acute intolerance syndrome is suspected.

Hypersensitivity reactions, which may include myocarditis and pericarditis, necessitate immediate evaluation and discontinuation of the medication if such reactions are suspected. Hepatic failure is another serious risk, particularly in patients with known liver impairment, who should be carefully assessed for the risks and benefits of treatment. Severe cutaneous adverse reactions warrant discontinuation at the first signs or symptoms, along with further evaluation for hypersensitivity. Patients should also be advised about photosensitivity, particularly those with pre-existing skin conditions, and should take precautions to avoid sun exposure.

Nephrolithiasis has been reported, with mesalamine-containing stones being undetectable by standard radiography or computed tomography (CT). Adequate hydration during treatment is crucial to mitigate this risk.

Additional important notes include the potential for spuriously elevated results in laboratory tests for urinary normetanephrine when using liquid chromatography with electrochemical detection in patients receiving Mesalamine Rectal Suppositories; alternative, selective assays for normetanephrine should be utilized. Patients with known or suspected hypersensitivity to salicylates or aminosalicylates, or to any ingredients in the formulation, should not use this medication.

Symptoms of salicylate toxicity, which may occur, include nausea, vomiting, abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms such as headache, dizziness, confusion, and seizures. Severe salicylate intoxication can lead to electrolyte and blood pH imbalances, potentially affecting other organs, including the kidneys and liver.

In clinical trials involving pediatric patients, adverse reactions such as abdominal pain, headache, pyrexia, pharyngolaryngeal pain, diarrhea, and vomiting were reported, mirroring those seen in adult patients. Furthermore, reports indicate a higher incidence of blood dyscrasias, including agranulocytosis, neutropenia, and pancytopenia, in patients aged 65 years and older receiving mesalamine-containing products compared to younger patients. Therefore, complete blood cell counts and platelet counts should be monitored in elderly patients during treatment.

Drug Interactions

The concomitant use of nephrotoxic agents, including nonsteroidal anti-inflammatory drugs (NSAIDs), with this medication may lead to an increased risk of nephrotoxicity. It is advisable to monitor renal function closely and observe for any mesalamine-related adverse reactions during co-administration.

When used in conjunction with azathioprine or 6-mercaptopurine, there is an elevated risk of blood disorders. Regular monitoring of complete blood cell counts and platelet counts is recommended to detect any potential hematological complications.

Packaging & NDC

The table below lists all NDC Code configurations of Mesalamine Rectal (mesalamine), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of Mesalamine Rectal Suppositories in pediatric patients for the treatment of mildly to moderately active ulcerative proctitis have not been established. A 6-week, open-label, single-arm study evaluated the use of Mesalamine Rectal Suppositories in 49 patients aged 5 to 17 years, of which only 14 had histologically-confirmed ulcerative proctitis. Efficacy was not demonstrated in this study.

Adverse reactions observed in pediatric patients included abdominal pain, headache, pyrexia, pharyngolaryngeal pain, diarrhea, and vomiting, which were similar to those reported in adult patients. Caution is advised when considering the use of this medication in the pediatric population due to the lack of established efficacy and safety data.

Geriatric Use

Clinical trials of Mesalamine Rectal Suppositories did not include a sufficient number of patients aged 65 years and older to determine whether they respond differently from younger patients. However, reports from uncontrolled clinical studies and postmarketing surveillance have indicated a higher incidence of blood dyscrasias, including agranulocytosis, neutropenia, and pancytopenia, in geriatric patients receiving mesalamine-containing products, such as Mesalamine Rectal Suppositories, compared to their younger counterparts.

Given these findings, it is essential to monitor complete blood cell counts and platelet counts in elderly patients during treatment with Mesalamine Rectal Suppositories. Additionally, when prescribing this medication to geriatric patients, healthcare providers should consider the increased likelihood of decreased hepatic, renal, or cardiac function, as well as the presence of concurrent diseases or other drug therapies that may affect treatment outcomes. Careful assessment and monitoring are recommended to ensure the safety and efficacy of Mesalamine Rectal Suppositories in this population.

Pregnancy

Limited published data on mesalamine use in pregnant patients are insufficient to inform a drug-associated risk. Animal studies have shown no evidence of teratogenicity when mesalamine was administered orally to rats or rabbits during gestation at doses greater than the recommended human intra-rectal dose. Specifically, reproduction studies conducted in rats at oral doses up to 320 mg/kg/day (approximately 1.7 times the recommended human intra-rectal dose based on body surface area) and in rabbits at doses up to 495 mg/kg/day (about 5.4 times the recommended human intra-rectal dose) during the period of organogenesis revealed no evidence of impaired fertility or harm to the fetus.

The estimated background risk of major birth defects and miscarriage for the indicated populations remains unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is approximately 2 to 4% and 15 to 20%, respectively. It is important to note that adverse outcomes in pregnancy can occur regardless of maternal health or medication use. Therefore, healthcare providers should carefully consider the potential benefits and risks of mesalamine when prescribing to pregnant patients or women of childbearing potential.

Lactation

Mesalamine and its N-acetyl metabolite are present in human milk in undetectable to small amounts. In published lactation studies, maternal mesalamine doses from various oral and rectal formulations ranged from 500 mg to 3 g daily. The concentration of mesalamine in milk ranged from non-detectable to 0.11 mg/L, while the concentration of the N-acetyl-5-aminosalicylic acid metabolite ranged from 5 to 18.1 mg/L. Based on these concentrations, estimated infant daily dosages for an exclusively breastfed infant are 0 to 0.017 mg/kg/day of mesalamine and 0.75 to 2.72 mg/kg/day of N-acetyl-5-aminosalicylic acid.

There are limited reports of diarrhea in breastfed infants, and lactating mothers should monitor breastfed infants for this adverse effect. There is no information on the effects of mesalamine on milk production. The lack of clinical data during lactation precludes a clear determination of the risk of Mesalamine Rectal Suppositories to an infant during lactation. Therefore, the developmental and health benefits of breastfeeding should be considered alongside the mother’s clinical need for Mesalamine Rectal Suppositories and any potential adverse effects on the breastfed child from the medication or from the underlying maternal conditions.

Renal Impairment

Patients with renal impairment or those taking nephrotoxic drugs should have their risks and benefits evaluated prior to treatment. It is essential to monitor renal function closely in these individuals. If there is any deterioration in renal function, Mesalamine Rectal Suppositories should be discontinued.

Hepatic Impairment

Patients with hepatic impairment should be carefully evaluated for the risks and benefits associated with treatment. It is essential to consider the degree of liver function compromise when determining the appropriateness of therapy. Monitoring of liver function tests may be necessary to assess the patient's condition and to guide treatment decisions. Adjustments to dosage or treatment regimens may be required based on the severity of hepatic impairment. Therefore, healthcare providers are advised to conduct a thorough assessment of liver function prior to initiating therapy in these patients.

Overdosage

In cases of mesalamine overdose, it is important to recognize that while mesalamine absorption from the colon is limited, the use of Mesalamine Rectal Suppositories can still lead to significant toxicity. Symptoms of salicylate toxicity may manifest as nausea, vomiting, and abdominal pain, along with respiratory symptoms such as tachypnea and hyperpnea. Neurologic symptoms, including headache, dizziness, confusion, and seizures, may also occur.

Severe salicylate intoxication can result in serious complications, including electrolyte and blood pH imbalances, which may further lead to involvement of other organs, such as the kidneys and liver.

Currently, there is no specific antidote available for mesalamine overdose. Management of an overdose should focus on correcting fluid and electrolyte imbalances through the administration of appropriate intravenous therapy. It is also crucial to monitor and maintain adequate renal function throughout the treatment process. Healthcare professionals should remain vigilant for the development of any severe symptoms and manage them accordingly.

Nonclinical Toxicology

Mesalamine was evaluated for its potential carcinogenicity in a two-year study involving Wistar rats. The results indicated no increase in the incidence of neoplastic lesions compared to controls at doses of up to 320 mg/kg/day, which is approximately 1.7 times the recommended human intra-rectal dose of Mesalamine Rectal Suppositories based on body surface area. Furthermore, mesalamine demonstrated no mutagenic effects in several assays, including the Ames test, the mouse lymphoma cell (TK +/-) forward mutation test, and the mouse micronucleus test.

In terms of reproductive toxicity, no adverse effects on fertility or reproductive performance were observed in male and female rats administered oral doses of mesalamine up to 320 mg/kg/day, again about 1.7 times the recommended human intra-rectal dose.

Toxicology studies conducted in various animal models, including rats, mice, rabbits, and dogs, identified the kidney as the primary target organ for toxicity. In rats, adverse renal effects were noted following a single oral dose of 600 mg/kg, approximately 3.2 times the recommended human intra-rectal dose, and at intravenous doses exceeding 214 mg/kg, about 1.2 times the recommended dose. A 13-week oral gavage toxicity study revealed papillary necrosis and/or multifocal tubular injury in male rats at a dose of 160 mg/kg, about 0.86 times the recommended dose, and in both sexes at 640 mg/kg, approximately 3.5 times the recommended dose.

In a combined 52-week toxicity and 127-week carcinogenicity study in rats, degeneration of the kidneys and hyalinization of basement membranes and Bowman’s capsule were observed at oral doses of 100 mg/kg/day, about 0.54 times the recommended dose, and higher. Conversely, a 14-day rectal toxicity study in rabbits showed that intra-rectal doses up to 800 mg/kg, approximately 8.6 times the recommended dose, did not result in any adverse effects.

In a six-month oral toxicity study in dogs, doses of 80 mg/kg, about 1.4 times the recommended dose, and higher were associated with renal pathology similar to that observed in rats. Additionally, a rectal toxicity study in dogs indicated that a dose of 166.6 mg/kg, approximately 3 times the recommended dose, led to chronic nephritis and pyelitis. Lastly, in a 12-month eye toxicity study in dogs, keratoconjunctivitis sicca (KCS) was noted at oral doses of 40 mg/kg, about 0.72 times the recommended dose, and above.

Postmarketing Experience

During post-approval use of Mesalamine Rectal Suppositories and other mesalamine-containing products, various adverse reactions have been reported voluntarily or through surveillance programs. Due to the nature of these reports, which originate from a population of uncertain size, it is not always feasible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse reactions identified include:

Body as a Whole: Reports of drug fever, fatigue, lupus-like syndrome, and medication residue have been noted.

Cardiac Disorders: Cases of myocarditis, pericarditis, and pericardial effusion have been documented.

Endocrine Disorders: Instances of nephrogenic diabetes insipidus have been reported.

Eye Disorders: Eye swelling has been observed.

Gastrointestinal Disorders: A range of gastrointestinal issues has been reported, including abdominal cramps, abdominal distension, anal pruritus, anorectal discomfort, constipation, discolored feces, flatulence, frequent bowel movements, gastrointestinal bleeding, mucus stools, nausea, painful defecation, pancreatitis, proctalgia, rectal discharge, rectal tenesmus, stomach discomfort, and vomiting.

Hepatic Disorders: Reports of cholestatic jaundice, hepatitis, jaundice, Kawasaki-like syndrome (including changes in liver enzymes), liver necrosis, and liver failure have been noted.

Hematologic Disorders: Cases of agranulocytosis, aplastic anemia, and thrombocytopenia have been documented.

Neurological/Psychiatric Disorders: Instances of Guillain-Barre syndrome, peripheral neuropathy, transverse myelitis, and intracranial hypertension have been reported.

Renal Disorders: Reports of interstitial nephritis, renal failure, minimal change disease, and nephrolithiasis have been observed.

Urine Discoloration: Discoloration of urine occurring ex-vivo has been noted due to contact of mesalamine, including its inactive metabolite, with surfaces or water treated with hypochlorite-containing bleach.

Respiratory, Thoracic and Mediastinal Disorders: Cases of hypersensitivity pneumonitis (including allergic alveolitis, eosinophilic pneumonitis, and interstitial pneumonitis) and pleuritis/pleurisy have been reported.

Skin and Subcutaneous Tissue Disorders: Adverse skin reactions include alopecia, erythema, erythema nodosum, pruritus, psoriasis, pyoderma gangrenosum, urticaria, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP).

Urogenital Disorders: Reversible oligospermia has been reported.

Patient Counseling

Patients should be advised to read the FDA-approved patient labeling (Patient Information) thoroughly to understand the proper use of Mesalamine Rectal Suppositories. It is important to instruct patients not to cut or break the suppository and to retain it for one to three hours, or longer if possible, to ensure optimal effectiveness.

Patients should be encouraged to drink an adequate amount of fluids during treatment. In the event that a dose of Mesalamine Rectal Suppositories is missed, patients should administer it as soon as possible, unless it is almost time for the next dose. They should be cautioned against using two suppositories at the same time to compensate for a missed dose.

Patients may notice that their urine becomes discolored reddish-brown while using Mesalamine Rectal Suppositories, particularly when it comes into contact with surfaces or water treated with hypochlorite-containing bleach. They should be advised to monitor their urine flow and report to their healthcare provider only if the discoloration occurs upon leaving the body, prior to contact with any surface or water.

It is essential to inform patients that Mesalamine Rectal Suppositories can stain direct contact surfaces, including fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel. Patients should be instructed to keep the suppositories away from these surfaces to prevent staining.

Patients should be made aware that Mesalamine Rectal Suppositories may decrease renal function, particularly in those with known renal impairment or those taking nephrotoxic drugs, including NSAIDs. Periodic monitoring of renal function will be conducted during therapy, and patients should be advised to complete all blood tests ordered by their healthcare provider.

Healthcare providers should inform patients about the signs and symptoms of hypersensitivity reactions. Patients should be instructed to discontinue use of Mesalamine Rectal Suppositories and report to their healthcare provider if they experience new or worsening symptoms of Acute Intolerance Syndrome, which may include cramping, abdominal pain, bloody diarrhea, fever, headache, malaise, conjunctivitis, and rash, or any other symptoms suggestive of mesalamine-induced hypersensitivity.

For patients with known liver disease, it is important to communicate the signs and symptoms of worsening liver function and advise them to report any such changes to their healthcare provider. Additionally, patients should be informed about the signs and symptoms of severe cutaneous adverse reactions and instructed to stop taking Mesalamine Rectal Suppositories and report to their healthcare provider at the first appearance of any severe cutaneous adverse reaction or other signs of hypersensitivity.

Patients with pre-existing skin conditions should be advised to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors. Furthermore, they should be instructed to drink an adequate amount of fluids during treatment to minimize the risk of kidney stone formation and to contact their healthcare provider if they experience signs or symptoms of a kidney stone, such as severe side or back pain or blood in the urine.

Finally, elderly patients and those taking azathioprine or 6-mercaptopurine should be informed of the risk for blood disorders and the necessity for periodic monitoring of complete blood cell counts and platelet counts while on therapy. They should be encouraged to complete all blood tests as directed by their healthcare provider.

Storage and Handling

The product is supplied in packaging that ensures its integrity and stability. It should be stored at temperatures below 25ºC (77ºF) and may be refrigerated if necessary. Care should be taken to keep the product away from direct heat, light, and humidity to maintain its efficacy and safety. Proper handling and storage conditions are essential to preserve the quality of the product throughout its shelf life.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Mesalamine Rectal as submitted by Amring Pharmaceuticals Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)